A strategy for high radioprotective activity via the assembly of the PprI protein with a ROS-sensitive polymeric carrier

With the rapid development and wide application of nuclear technology, radiation hazards present an enormous challenge for biological and medical safety. Currently, one of the major challenges in radiation protection is the discovery of more effective and less toxic radioprotectant agents. Herein, we present a strategy for high radioprotective activity via the assembly of the PprI protein with a reactive oxygen species (ROS)-sensitive polymeric carrier. The graft copolymer CS–CP₅K–PEG is synthesized via the reaction of PEG–CP₅K–NHS and CS, which is used for the assembly of the PprI protein. The assembly complex is less toxic to human cells and more stable to enzymatic cleavage than the PprI protein. The ROS degradability of the CS–CP₅K–PEG polymer is confirmed via the SIN-1 mediated cleavage of CP₅K peptide linkers through the shift in their GPC chromatogram. The radioprotection activity of the assembly complex is remarkably improved both in HUVECs and C57BL/6 mice compared to that of the PprI protein, showing more beneficial effects than the PprI protein. Thus, this work may provide a new approach for highly effective radioprotection.